Abstract: Objective: To evaluate the beneficial effect of the therapeutic regimen supplemented with vitamin D3 (VD3) on chronic spontaneous urticaria (CSU). Methods: From Oct.2017 to Oct, 2018, 90 patients with CSU, 21 patients with chronic inducible urticaria (CIndU) and 55 healthy subjects were recruited from Department of Dermatology, Renmin Hospital of Wuhan University. Routine laboratory tests including the levels of serum 25-(OH)D3, plasma D-dimer, fibrin degradation products (FDP) and erythrocyte sedimentation rate (ESR) were carried out, meanwhile, the urticaria activity score 7 (UAS7) was recorded for each patients at baseline and each follow-up . Peripheral blood mononuclear cells (PBMCs) were collected and purified from 15 CSU patients and 15 healthy subjects. PBMCs were cultured with fresh complete RPMI 1640 medium containing 10 μg/mL phytohaemagglutinin (PHA) and treated with 1α,25- (OH)2D3 at varying concentrations. After treatment, the cells were harvested and used for measuring the mRNA levels of IL-6 and vitamin D receptor (VDR) using real-time fluorescent quantitative PCR (qPCR). CSU patients with severe VD3 deficiency (less than 10 ng/mL of serum 25-(OH)D3) were treated with 2400 IU VD3 per day, the patients with VD3 deficiency (10-20 ng/mL of serum 25-(OH)D3) were treated with 800 IU VD3 per day. The patients without VD3 treatment served as negative control. All patients were assessed by UAS7 at 6 and 12 weeks post-treatment. Results: The levels of serum 25-(OH)D3 were significantly lower in the patients with CSU as compared with the healthy controls. The levels of D-dimer, FDP, ESR were significantly higher than the healthy controls. The increases in the levels of D-dimer, FDP, and ESR were also positively correlated with the UAS7 assessment. qPCR results showed that the transcript levels of IL-6 and VDR were elevated in PBMC derived from 15 CSU patients in comparison with the healthy controls.The decreased IL-6 levels and enhanced VDR levels were observed in the PBMCs exposed to 1α,25-(OH)2D3,all P<0.05. Moreover, we also found that UAS7 score was much lower in patients with severe VD3 deficiency and  treated with VD3 than that in untreated controls at 12 weeks post-treatment, P<0.0001.Conclusion: VD3 supplement may be beneficial for resolving the clinical symptoms of CSU, possibly through its inhibition of subclinical inflammation in urticaria.

Key words: chronic spontaneous urticaria, vitamin D3, subclinical inflammation